Brn3b regulates the formation of fear-related midbrain circuits and defensive responses to visual threat.

Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the development and function of these circuits remain unresolved. Here, we show that midbrain-specific deletion of the transcription factor Brn3b causes a loss of neurons projecting to the lateral posterior nucleus of the thalamus. Brn3b deletion also down-regulates the expression of the neuropeptide tachykinin 2 (Tac2). Furthermore, Brn3b mutant mice display impaired defensive freezing responses to visual threat precipitated by social isolation. This behavioral phenotype could be ameliorated by overexpressing Tac2, suggesting that Tac2 acts downstream of Brn3b in regulating defensive responses to threat. Together, our experiments identify specific genetic components critical for the functional organization of midbrain fear-related visual circuits. Similar mechanisms may contribute to the development and function of additional long-range brain circuits underlying fear-associated behavior.

BIPOC experiences of (anti-)racist patient engagement in adolescent and young adult oncology research: an electronic Delphi study.

Aims: To characterize Black, Indigenous and People of Color (BIPOC) adolescent and young adult (AYA) cancer patients' experiences of patient engagement in AYA oncology and derive best practices that are co-developed by BIPOC AYAs and oncology professionals. Materials & methods: Following a previous call to action from AYA oncology professionals, a panel of experts composed exclusively of BIPOC AYA cancer patients (n = 32) participated in an electronic Delphi study. Results: Emergent themes described BIPOC AYA cancer patients' direct experiences and consensus opinion on recommendations to advance antiracist patient engagement from BIPOC AYA cancer patients and oncology professionals. Conclusion: The findings reveal high-priority practices across all phases of research and are instructional for advancing health equity.

Rorß regulates selective axon-target innervation in the mammalian midbrain.

Developmental control of long-range neuronal connections in the mammalian midbrain remains unclear. We explored the mechanisms regulating target selection of the developing superior colliculus (SC). The SC is a midbrain center that directs orienting behaviors and defense responses. We discovered that a transcription factor, Rorß, controls establishment of axonal projections from the SC to two thalamic nuclei: the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior nucleus (LP). A genetic strategy used to visualize SC circuits revealed that in control animals Rorß+ neurons abundantly innervate the dLGN but barely innervate the LP. The opposite phenotype was observed in global and conditional Rorb mutants: projections to the dLGN were strongly decreased, and projections to the LP were increased. Furthermore, overexpression of Rorb in the wild type showed increased projections to the dLGN and decreased projections to the LP. In summary, we identified Rorß as a key developmental mediator of colliculo-thalamic innervation. Such regulation could represent a general mechanism orchestrating long-range neuronal connections in the mammalian brain.

Marination and Physicochemical Characteristics of Vacuum-aged Duck Breast Meat.

We investigated marinade absorption and physicochemical characteristics of vacuum-aged duck breasts that were halved and individually vacuum-packed for chiller aging at 4°C for 14 d. One half was marinated for 0, 7, or 14 d, while the second half was used as a control. Marinade absorption, cooking loss, cooking yield, texture profile, pH, color, protein solubility, and thiobarbituric acid reactive substances (TBARS) values were evaluated, and protein sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed. Marinade absorption and pH did not vary significantly after 14 d of aging. Marination increased the pH, color (a* and b*) values, and cooking yield and reduced cooking loss. TBARS values significantly increased with aging time, but were significantly reduced by marination. Myofibril and total protein solubility increased with aging and marination, while SDS-PAGE showed protein degradation. Hence, aging and marination can be used simultaneously to improve physicochemical quality and cooking yield of vacuum-aged duck breast.

Effects of individualized versus group task-oriented circuit training on balance ability and gait endurance in chronic stroke inpatients.

[Purpose] The purpose of this study was to analyze the effects of task-oriented circuit training on the balance ability and gait endurance of chronic stroke inpatients. [Subjects and Methods] The participants were 30 patients who had stroke >6 months previously, resulting in a disability such as hemiparesis. The participants were randomly divided into the group task-oriented circuit training group and the individual task-oriented circuit-training group. They performed eight types of modified task-oriented training. Balance ability and gait endurance were measured by using the Berg balance scale questionnaire and the 6-min walk test, respectively, before and after the experiment. [Results] Significant differences were observed between before and after the intervention in all variables. There was a significant difference between groups in Berg balance scale scores; however, no significant differences were seen in the timed up and go test and the 6-min walk test. [Conclusion] The results of this study indicated that group exercise can better improve the balance ability of chronic stroke inpatients after stroke than can individualized exercise intervention.

Provider preparedness to care for sexual and gender minority adolescent and young adult cancer patients: A scoping review.

Objective: The purpose of the current scoping review is to explore knowledge and gaps in the literature on the preparedness of health care providers (HCPs) to deliver cancer care that addresses the needs of sexual and gender minority (SGM) adolescent and young adult (AYA) patients diagnosed with cancer between ages 15-39 years. Methods: We conducted two comprehensive searches on OVID MEDLINE, PsycINFO, and CINAHL in February 2022 and June 2024; examined the empirical literature on HCPs who treat SGM AYA cancer patients; characterized existing research; and evaluated each contribution. Results: A total of thirteen articles were included in the final review. The reviewed studies varied widely in sample sizes (n = 6 to n = 1253), reflecting different methodological approaches: quantitative cross-sectional (n = 3), qualitative (n = 4), and mixed methods (n = 6). Innovation: The current scoping review piloted an innovative Quality Assessment (QA) Tool of Foundational Progress for SGM AYA Research to assess the quality of evidence, providing a new framework for evaluating and guiding future research. Conclusion: The existing literature on provider preparedness to care for SGM AYA cancer patients is limited. Future studies are critically needed to improve providers' ability to holistically respond to the unique health care needs and concerns of this population.

Disparities in cancer care among sexual and gender minority adolescent and young adult patients: A scoping review.

BACKGROUND: Adolescent and young adult cancer patients (AYAs) who are sexual and gender minorities (SGM) are a rapidly increasing population that experiences unmet cancer-related needs. Despite emerging awareness, little is known about cancer care and outcomes for this vulnerable population. The purpose of this scoping review was to explore current knowledge and gaps in the literature on cancer care and outcomes for AYAs who identify as SGM. METHODS: We reviewed empirical knowledge on SGM AYAs by identifying, describing, and critically appraising the literature to date. We conducted a comprehensive search on OVID MEDLINE, PsycINFO, and CINAHL in February 2022. Additionally, we developed and piloted a conceptual framework for appraising SGM AYA research. RESULTS: A total of 37 articles were included in the final review. Most studies focused exclusively on SGM-related outcomes as the primary aim of the study (81.1%, n = 30), whereas others included some focus on SGM-related outcomes (18.9%, n = 7). The majority of studies included AYAs as part of a broader age range (86.0%, n = 32), and only a few studies examined exclusively AYA samples (14.0%, n = 5). Gaps in scientific evidence on SGM AYAs were seen across the cancer care continuum. CONCLUSION: Numerous gaps in knowledge of cancer care and outcomes exist for SGM AYAs diagnosed with cancer. Future efforts should fill this void with high-quality empirical studies that reveal unknown disparities in care and outcomes and are inclusive of the intersectionality of SGM AYAs with other minoritized experiences, thereby advancing health equity in meaningful ways.

Anticipatory Guidance: Developing a Patient Navigation Pathway to Reduce the Financial Toxicity of Cancer.

Background: Healthcare providers have an influential role in the experience of financial toxicity among their cancer patients, yet patients commonly report unmet needs and dissatisfaction regarding communication with their providers about financial concerns. Aims: The purpose of this study is to develop a novel financial navigation pathway that leverages existing patient financial services and resources with corresponding patient-centered, community-informed strategies, via study participants, that may be utilized in routine care to reduce financial hardship among cancer patients. Methods: We conducted in-depth interviews (n=50) with 34 cancer patients and 16 cancer care professionals at a National Cancer Institute designated comprehensive cancer center located in a dense urban area of the US between December2022 to June 2023. Results: Content analyses resulted in emergent themes and representative quotations on experiences of financial hardship within the material, behavioral, and psychosocial domains. Investigators used emergent themes to develop financial strategies and construct a financial navigation pathway to screen patients for and intervene upon the financial toxicity of cancer in routine care. Conclusion: This study followed an innovative approach by constructing a financial navigation pathway tool that follows the oncological workflow at a National Cancer Institute designated comprehensive cancer center. Future research is needed to test the tool's impact on financial toxicity, cancer outcomes, and other health-related outcomes, and to better understand how much patient navigation is needed to bring about meaningful change.

Gene duplication and loss in a MADS box gene transcription factor circuit.

Although many models have been proposed that could lead to the maintenance of gene duplicates, the ways in which interacting gene duplicates influence each other's evolution and function remain poorly understood. Here, we focus on duplication and loss of the B class MADS box transcription factor genes in the euasterids I and the ramifications of such changes on paralog evolution and their encoded functions. In core eudicots, the B class genes belong to two paralogous lineages whose products form obligate heterodimers. Based on comparative genomic and phylogenetic analyses, we show that five stepwise B class MADS box gene gain or loss events occurred during the radiation of the euasterids I within core eudicots. Gene loss in one sublineage was correlated with a deficit of other sublineage genes. We also show that the gain or loss of B class MADS box gene paralogs were associated with altered protein-protein interactions among the remaining copies. These altered protein interactions were correlated with asymmetric patterns of sequence diversification and selection, suggesting that compensatory changes were driving the evolution of such genes. Furthermore, these B class MADS box gene gain or loss events were associated with the evolutionary divergence of floral morphology in the euasterids I. Together, these observations point to a cooperative strategy by which gene networks evolve, with selection maintaining the overall logic of a network despite changes in individual components.

Effect of Combined Exercise Program on Lower Extremity Alignment and Knee Pain in Patients with Genu Varum.

This study aimed to assess the effect of a combined exercise program on lower-extremity alignment and knee pain in patients with genu varum. Forty-seven middle-aged women with knee pain and genu varum were randomly divided into the exercise (EG, n = 24) and control (CG, n = 23) groups. The exercise group underwent a combined exercise program lasting 60 min in one session, three times a week for 12 weeks. Knee-to-knee length (KTKL), hip-knee-ankle angle (HKAA), hip inclination angle (HIA), and medial proximal tibial angle (MPTA) were assessed to evaluate lower-extremity alignment. To evaluate knee pain, the short form-McGill Pain Questionnaire (SF-MPQ) were used. There was a significant difference between the groups, and a decrease of 16% in KTKL (from 6.48 ± 1.26 cm to 5.47 ± 1.21 cm) was shown in EG. Other variables, including HKAA, HIA, and MPTA on the right side, showed significant differences between pre- and post-intervention in EG (p < 0.01, p < 0.01, and p < 0.01, respectively). SF-MPQ score improved with 45% from 18.75 ± 1.64 to 10.33 ± 2.47 after exercise intervention in EG. These results suggest that the combined exercise program, including strength and neuromuscular exercises, is an effective intervention for improving lower-extremity alignment and knee pain in middle-aged women with genu varum.

Association between the dietary inflammatory index and bone markers in postmenopausal women.

INTRODUCTION: The health problem of postmenopausal women is emerging as an important problem due to the increased aging population. This study investigated the association between dietary inflammatory index (DII) and bone markers in postmenopausal women. METHODS: A cross-sectional study was conducted on 132 postmenopausal women aged 45-70 years. The DII score was calculated using the 3-day food records and divided into tertiles according to the DII score. The lifestyle factors that could affect bone mineral density (BMD) in postmenopausal women were investigated and included the EuroQol- 5 Dimension (EQ-5D), physical activity, and eating habits. Skeletal muscle index-weight (SMIw) was used to evaluate skeletal muscle mass, and alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BSALP), and phosphorus (P) measured as bone biomarkers. The BMD was measured using dual-energy X-ray absorptiometry, and the association between anthropometric, biochemistry, BMD, and DII was assessed. RESULTS: In the anti-inflammatory group, a high intake of fiber, vitamins, and minerals was observed. After adjusting for confound factors, with higher DII score, percent body fat increased (ß = 0.168, p = 0.012), and SMIw decreased linear regression analysis (ß = -0.329, p = 0.037, respectively). For biochemistry, confound factors were adjusted, with higher DII score, ALP, BSALP and P decreased and DII score increased (ß = -0.057, p = 0.002, ß = -0.167, p = 0.004, ß = -1.799, p = 0.026, respectively). The relationship between DII and BMD was not significant, but osteopenia increased as DII score increased. CONCLUSION: The low DII score is positively associated with low body fat, high muscle mass, elevated bone markers, and low risk of osteopenia.

Interventional benefit of Pilates using Oov and mat on middle-aged women with lower urinary tract symptoms: emphasis on abdominal muscle thickness and muscular function.

Lower urinary tract symptoms (LUTS) have been considered as clinically prevalent symptom in women, and can be ameliorated by the change of abdominal muscles and pelvic floor muscle (PFM). This study investigated the efficacy of Pilates program using Oov and mat on the change of abdominal muscle thickness, PFM function, and LUTS clinical score. 53 women experiencing LUTS were randomly assigned to Oov Pilates exercise group (OPEG) (n=20), mat Pilates exercise group (MPEG) (n= 16), and symptomatic control group (SCG) (n=17), respectively, and two groups using Oov and mat participated in 8-week Pilates program. Thickness of abdominal muscle, functional movement of PFM, and LUTS clinical score were measured from all groups. Thickness of rectus abdominis, internal oblique abdominis, transversus abdominis was significantly improved in OPEG (P<0.05), however, MPEG showed a significant change only in transversus abdominis (P<0.05). In all abdominal muscles, OPEG had a significantly improved abdominal muscle thickness compared to SCG (P<0.05). Functional movement of PFM in OPEG was significantly decreased (P<0.005), but not in MPEG and SCG. In LUTS clinical score, OPEG and MPEG showed a significantly abated symptoms in degree of voiding-related symptoms and discomfort (P<0.005), but not in SCG. Our study highlighted that Pilates using Oov can be an effective intervention to ameliorate the quantitative quality of abdominal muscle thickness and PFM, which ultimately provides the satisfied self-clinical index in degree of voiding-related symptoms and discomfort.

The Efficacy of Pilates on Urinary Incontinence in Korean Women: A Metabolomics Approach.

Pilates has been known as exercise intervention that improves the function of pelvic floor muscle (PFM) associated with impacting urinary incontinence (UI). This study investigated the effect of Pilates on UI in Korean women by determining the change in functional movement of PFM (FMP) and metabolic profiles. UI group with Pilates (UIP, n = 13) participated in 8-weeks Oov Pilates program, and 8 subjects were assigned to Control and UI group with no Pilates (UINP), respectively. Before and after 8 weeks, plasma samples were collected from all participants, and ultrasonography was used to measure the functional change of PFM for calculating FMP ratio. Plasma samples were analyzed by mass spectrometry to identify the change of metabolic features. After 8-weeks intervention, FMP ratio was remarkably decreased in UIP (48.1% ↓, p < 0.001), but not in Control and UINP (p > 0.05). In metabolic features, L-Glutamine (m/z: 147.07 [M + H]+), L-Cystathionine (m/z: 240.09 [M + NH4]+), L-Arginine (m/z: 197.1 [M + Na]+), and L-1-Pyrroline-3-hydroxy-5-carboxylate (m/z: 147.07 [M + NH4]+) were significantly elevated solely in UIP (p < 0.001). Our study elucidated that Pilates can ameliorate the FMP and enhance the specific metabolic characteristics, which was potentially associated with invigorated PFM contractility to effectively control the bladder base and continence.

Comparative Analysis of Lenvatinib and Hepatic Arterial Infusion Chemotherapy in Unresectable Hepatocellular Carcinoma: A Multi-Center, Propensity Score Study.

The comparative efficacy and safety between lenvatinib and hepatic artery infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC) is still unclear. This multicenter historical cohort study enrolled 244 patients who were treated with HAIC (n = 173) or lenvatinib (n = 71) between 2012 and 2020. Propensity score matching (PSM) was performed, and 52 patients were selected per group. Clinical outcomes and safety were compared. Objective response rate (ORR) was not different between the two groups (26.0% vs. 23.1%, p = 0.736). Before PSM, the HAIC group had a higher proportion of Child-Pugh B and portal vein tumor, whereas the lenvatinib group had more patients with extrahepatic metastases, which was adjusted after PSM. There were no differences in progression-free survival (PFS) and overall survival (OS) after PSM (HAIC vs. lenvatinib, median PFS, 3.6 vs. 4.0 months, p = 0.706; median OS 10.8 vs. 7.9 months, p = 0.106). Multivariate Cox-regression showed that alpha-fetoprotein ≤1000 ng/mL was only an associated factor for OS after PSM in all patients (hazard ratio = 0.421, p = 0.011). Subgroup analysis for patients with a high tumor burden beyond the REFLECT eligibility criteria revealed that the HAIC group (n = 29) had a significantly longer OS than did the lenvatinib group (n = 30) (10.0 vs. 5.4 months, p = 0.004). More patients in the HAIC group achieved better liver function than those in the lenvatinib group at the time of best responses. There was no difference in the incidence of grade 3 and 4 adverse events between the two groups. Therefore, lenvatinib is comparable to HAIC in terms of ORR and OS in unresectable HCC meeting REFLECT eligibility criteria.

Connectomic analysis reveals an interneuron with an integral role in the retinal circuit for night vision.

Night vision in mammals depends fundamentally on rod photoreceptors and the well-studied rod bipolar (RB) cell pathway. The central neuron in this pathway, the AII amacrine cell (AC), exhibits a spatially tuned receptive field, composed of an excitatory center and an inhibitory surround, that propagates to ganglion cells, the retina's projection neurons. The circuitry underlying the surround of the AII, however, remains unresolved. Here, we combined structural, functional and optogenetic analyses of the mouse retina to discover that surround inhibition of the AII depends primarily on a single interneuron type, the NOS-1 AC: a multistratified, axon-bearing GABAergic cell, with dendrites in both ON and OFF synaptic layers, but with a pure ON (depolarizing) response to light. Our study demonstrates generally that novel neural circuits can be identified from targeted connectomic analyses and specifically that the NOS-1 AC mediates long-range inhibition during night vision and is a major element of the RB pathway.

The effects of a community-based walking program on walking ability and fall-related self-efficacy of chronic stroke patients.

The objectives of this study were to evaluate the effects of community-based walking training (CWT) on the walking ability and fall-related self-efficacy of chronic stroke patients and compare the effects of CWT to the conventional walking programs in stroke patients. Previous studies focused on walking speed, walking endurance, and balance. However, no studies have examined the changes in fall-related self-efficacy after CWT. In order to achieve purpose of this study, 45 chronic stroke patients, who were hospitalized at National Rehabilitation Center, were randomly divided into the CWT group (CWTG, n=15), the treadmill walking training group (TWTG, n=15), and the control group (CG, n=15). The treatment was conducted 3 times per week (30 min each) for 4 weeks. CWT was carried out by gradually increasing the difficulty level in various environments outside the hospital room. The results revealed that the CWTG was more effective in enhancing the walking ability and fall-related self-efficacy than the TWTG and the CG. These findings demonstrated that the CWTG increased the walking ability and fall-related self-efficacy of chronic stroke patients. Therefore, we suggest that adding CWT to standard rehabilitation might be an effective method for improving walking ability and fall-related self-efficacy in chronic stroke patients.

Effect of 8-week Nordic walking training on nondominant hand grip and shoulder strength in middle-aged women.

Nordic walking (NW) is a full body training that can be performed with special pole, and has been recognized as an effective out-door activity which can improve the strength of upper extremity. Most previous studies mainly analyzed the effect of NW on the strength of dominant (DN) hand-grip strength, however, a clear scientific examination is needed whether nondominant (NDN) extremity can also be ameliorated by the NW. Therefore, the aim of our study is to investigate the effectiveness of 8 weeks NW training on the NDN handgrip and shoulder strength in healthy middle-aged women. 29 subjects were randomly divided into three groups: Nordic walking group (NWG, n=10), brisk walking group (BWG, n=11), and control group (CG, n=8). Handgrip and shoulder strength were measured by the hand dynamometer and isokinetic machine. NW training was performed 3 times a week, and had 10-min warm-up, 40-min main program consisted of ALFA (Attention, Long arms, Flat poles, Adaptes) technique and Turbo walking, and 10-min cool-down. In handgrip strength of DN hand and the shoulder flexor strength in the both sides, NWG and BWG showed significantly higher value compared to CG. In the NDN hand, NWG also showed significantly higher strength compared to CG, however, there was no significant difference in the handgrip strength/weight among groups. In NDN shoulder extension, significantly higher improvement was found in NWG and BWG compared to that of CG. In conclusion, our study showed that NW can improve the strength of upper extremity in subjects, and can be better approach to improve the NDN handgrip strength than brisk walking method could.

Uhrf1 regulates active transcriptional marks at bivalent domains in pluripotent stem cells through Setd1a.

Embryonic stem cells (ESCs) maintain pluripotency through unique epigenetic states. When ESCs commit to a specific lineage, epigenetic changes in histones and DNA accompany the transition to specialized cell types. Investigating how epigenetic regulation controls lineage specification is critical in order to generate the required cell types for clinical applications. Uhrf1 is a widely known hemi-methylated DNA-binding protein, playing a role in DNA methylation through the recruitment of Dnmt1 and in heterochromatin formation alongside G9a, Trim28, and HDACs. Although Uhrf1 is not essential in ESC self-renewal, it remains elusive how Uhrf1 regulates cell specification. Here we report that Uhrf1 forms a complex with the active trithorax group, the Setd1a/COMPASS complex, to maintain bivalent histone marks, particularly those associated with neuroectoderm and mesoderm specification. Overall, our data demonstrate that Uhrf1 safeguards proper differentiation via bivalent histone modifications.

Effects of taping therapy for carpal space expansion on electrophysiological change in patients with carpal tunnel syndrome.

Taping therapy is one of the most conservative treatments for carpal tunnel syndrome (CTS). Preceding research studied on pain control, grip strength, and wrist function but no studies have been reported on electrophysiolgical changes after taping therapy. The aim of this study is to evaluate the effects of taping therapy for carpal space expansion on electrophysiological in 20 female patients aged from 40s to 60s with CTS. Experimental group applied taping therapy for carpal space expansion twice a week for 4 weeks and control group did not. There were significant differences between distal motor latency (DML) and sensory nerve conduction velocity (SNCV), but no difference between compound muscle action potential and sensory nerve action potential (SNAP) after 4 weeks taping treatment. Also, there was a significant difference in DML, SNCV, and SNAP in between groups. In conclusion, taping therapy for carpal space expansion can help to reduce the pressure of the carpal tunnel in CTS patients with mild symptoms.

Flexible thin-layer plasma inactivation of bacteria and mold survival in beef jerky packaging and its effects on the meat's physicochemical properties.

The aims of the present study were to examine the use of a flexible thin-layer plasma system in inactivating bacteria and mold on beef jerky in a commercial package and to evaluate the physicochemical changes of the jerky. After plasma treatment for 10min, Escherichia coli O157:H7, Listeria monocytogenes, Salmonella Typhimurium, and Aspergillus flavus populations on the beef jerky were reduced by approximately 2 to 3Log CFU/g. No significant changes in metmyoglobin content, shear force, and myofibrillar fragmentation index were found in the plasma-treated beef jerky. On the other hand, the peroxide content and L⁎ value were decreased whereas the a⁎ and ΔE value were increased in the plasma-treated sample. Sensory evaluation indicated negative effects of plasma treatment on flavor, off-odor, and overall acceptability of the beef jerky. In conclusion, the flexible thin-layer plasma system could be employed as a means for decontamination of beef jerky, with slight changes to the physicochemical quality of the product.